With the landing force of U.S. Navy sailors and United States Marines, Germantown′s detachment crossed the bar on 18 April 1847 and successfully stormed the Mexican fortifications.

As "a point of honor as well as duty," they reclaimed guns and ordnance stores, seized by the Mexicans from the wrecked brig USS Truxtun.

She returned to Veracruz on 9 July 1848 and, after receiving government dispatches, she departed Punta de Antón Lizardo on 29 August 1848 and sailed to Pensacola, Florida, where she arrived on 12 September 1848.

After touching at Key West, Florida, and Norfolk, she resumed her station off St. Thomas on 10 February 1850 and protected American commerce in the Caribbean until again ordered to the United States on 8 August 1850.

Operating out of Porto Praya with the sloops-of-war Dale and John Adams and the brigs Perry and Porpoise, she spent almost the next two years cruising the South Atlantic Ocean to St. Helena Island and along the African coast from Cape Mesurado to Loando, Portuguese West Africa.

During this time the squadron "rendered aid to our countrymen, gave protection to our commerce, and security to the emigrants and missionaries located on the coast, and as far as practicable," reported Commodore La Vallette, "checked the slave traders in their abominable traffic."

During much of 1855 she maintained station off Montevideo, Uruguay, where political disturbances and revolutionary activities threatened the lives and property of foreign nationals.

During an insurrection three months later a landing party of sailors and Marines under Lieutenant A. S. Nicholson assisted forces from ships of three other countries in guarding consulates and the custom house.

Departing Norfolk on 4 August 1857, she sailed via the Cape of Good Hope to Ceylon, where on 22 December 1857 she joined Flag Officer Josiah Tattnall III's East India Squadron off Point de Gala.